Research in the area of prosthetic devices formed from polymeric materials has been vigorous, generally having the espoused purpose of locating polymers which are compatible in physiological environments and which can be used to form prosthetic devices which maintain their structural integrity over long periods of time. With respect to research in the area of urological prostheses, however, a thorny problem arises in that, due to the high salt content of urinary fluids, calcium encrustation of polymeric prostheses takes place and builds up over time such that the bladder is "choked off", or scaled such that the use of these devices for long term periods has been generally foreclosed. The present invention remedies this drawback by grafting to or interpenetrating with the surface of any prosthetic urological device a thin layer of a hydrogel copolymer comprised of poly (2-hydroxyethyl methacrylate), pHEMA. The unique manner in which artificial bladders constructed in accordance with the principles of the present invention will be subsequently detailed.
Hydrogel prostheses made of pHEMA have demonstrated resistance to calcification in the urinary tract (Block et al, Trans. Amer. Soc. Art. Int. Organs., 23, 367, 1977; Kocvara et al, J. Biomed. Mat. Res., 2, 489, 1967; Levowitz et al, Trans. Amer. Soc. Art. Int. Organs., 14, 82, 1968). Recent data suggests that the methacrylic acid, MAA, content in these gels plays a critical role in their urine compatibility. It is also well known that the equilibrium water content and other properties of the gel change significantly according to MAA content (Ilavsky et al, J. Appl. Polym. Sci., 23, 2073, 1979).
Articles used in medical applications which have been fabricated in bulk from hydrogels such as copolymers of pHEMA and MAA are known. For example, U.S. Pat. No. 2,976,576 to Wichterle discloses shaped three-dimensional articles formed wholly of a polymer which may be fabricated in part from a glycol monomethacrylate copolymerized with MAA. The advantages pointed out derive chiefly from the fact that the polymers are resistant to chemical attack and have colloidal properties making them compatible with living tissue and membranes. The polymer is described as having the capability of swelling in solution. Similarly, U.S. Pat. No. 3,220,960, also to Wichterle, discloses cross-linked hydrophilic polymers compatible with physiological environments and articles made therefrom, which polymers form hydrogels that are capable of being elastically deformed by swelling with water.
U.S. Pat. No. 3,520,949 to Shepherd discloses hydrophilic polymers based on hydroxyalkyl methacrylates used as flavor or essence carriers and discloses that the polymers have reversible fluid absorption properties. The polymers are stated to be chemically and physically inert. U.S. Pat. No. 3,566,874, also to Shepherd, a continuation-in-part of the aforementioned U.S. Pat. No. 3,520,949, discloses catheters coated with polymers which may be fabricated from lower hydroxyalkyl acrylates and which may be used as a carrier for an antibiotic or germicide to reduce the risk of infection.
U.S. Pat. No. 4,076,921 to Stol discloses glycol acrylates or glycol methacrylates which may be copolymerized with methacrylic acid and crosslinked with glycol dimethacrylates. Use of the polymer as a prosthetic material is noted.
None of the preceeding documents disclose, however, that calcium encrustation of the surface of a urinary bladder or other urinary tract prostheses can be effectively dealt with on a continuous and ongoing basis over long periods of time in the manner developed by the present inventors. None of these references provide details of the effects of low levels of MAA, i.e. less than 4 mole fraction %, on the swelling behavior of gels having a crosslinker content less than 0.5%. For that matter, much of the research in the area of hydrogels has been bottomed on the knowledge that swelling behavior in largely dependent on the amount of ionizable species (e.g. MAA) in the polymer. Much of this research, therefore, can perhaps be characterized by the attitude that if "some is good, more is better".
Further, the present inventors have discovered that a phenomenon known as "polymer collapse" can be used to great advantage to solve the problem of calcium encrustation by grafting or surface interpenetrating a thin layer of a pHEMA-MAA cross-linked copolymer system onto a substantially physically and chemically inert substance used to form a urological prothesis. The term "polymer collapse" refers to the phenomenon whereby hydrogels are characterized by certain equilibrium volumes depending on the aqueous environment into which they are placed. As environmental conditions change, e.g., salt concentration, pH, etc., this equilibrium volume also changes with time. The term "polymer collapse" refers only to the fact that a hydrogel may be swollen depending upon its aqueous environment, but does not imply anything with respect to temporal suddenness, i.e. the amount of time which is required for the gel equilibrium volume to change.
Recent research on polymer collapse by Tanaka et al (Scattering Techniques Applied to Supramolecular and Nonequilibrium Systems, Ed. S-H. Chin, B. Chu, R. Nossal., Plenum, New York 1981) shows that the gel volume is the result of three constituent forces that set the osmotic pressure within the gel. These forces are (1) the rubber-like elasticity, (2) polymer-polymer affinity and (3) hydrogen-ion pressure. Tanaka et al showed that when environmental factors such as pH, electrolyte or solvent concentration are plotted against a property of a gel such as swelling or water content, the curve describing the transition of the polymer from a swollen state to a contracted state, or vice-versa, may be continuous, corresponding to shrinkage, or discontinuous corresponding to collapse of the gel. These events pertain, as previously described, to the equilibrium volume of the gel and not to the time required to reach equilibrium swelling. As volume changes are tied to diffusive rearrangement of the polymer structure, changes of state can be quite lengthy for bulk gels. Experiments show that bulk gels with normal levels of crosslinker (greater than 0.5%) that are 2-3 mm in thickness may require as long as 2-3 days at 40.degree. C. to reach equilibrium. Similarly sized bulk gels doped with MAA and with smaller levels of crosslinker require only 2-3 hours at 40.degree. C. to reach equilibrium. The inventors have now discovered that significantly faster changes occur for surface zones or for thin grafted layers which, having thicknesses on the orders of microns, can respond to local environmental changes within seconds.